Q1 2023 Fulcrum Therapeutics Inc Earnings Call
Good morning, and welcome to the Fulcrum Therapeutics first quarter 'twenty to 'twenty, three financial results and business.
Update conference call. Currently all participants are in a listen only mode. This call is being webcast live on the investors section.
All comes website at W. W. W. Dot Fulcrum T X dotcom and is being recorded for.
For opening remarks, I would like to introduce Chris Calvert Breeze. Please go ahead.
Thank you and good morning, welcome to the Fulcrum Therapeutics first quarter 2023 financial results and business update conference call. Please be reminded that remarks made during this call may contain forward looking statements within the meaning of the private Securities Litigation Reform Act of 1995.
These may include statements about the company's future expectations and plans, including the clinical hold of SPX 60, 58 clinical development timelines and financial projections. While these forward looking statements represent <unk> views as of today, they should not be relied upon as representing the company's views in the future.
Booker May update these statements in the future, but it's not taking on an obligation to do so please refer to <unk>. Most recent filings with the Securities and Exchange Commission for a discussion of certain risks and uncertainties associated with the company's business, leading the call today will be Dr. Robert Gould interim Chief Executive Officer.
Sure Paul Krump, who will provide a corporate overview discuss key pipeline updates as well as the financials before we open the call for Q&A and Doctor Ian Frazier interim Chief Medical officer will be able to answer questions. During the Q&A portion of the call with that it's my pleasure to turn the call over to Robert.
Thank you Chris Good morning, I appreciate everyone, taking the time to join us today.
I'd like to begin by reiterating our deep commitment to advancing our organization and improving the lives of patients with genetically defined diseases in areas of high unmet medical need.
In the first few months of 2023, we continue to make progress to address the ft at $60 58, clinical hold and advance our phase III reach trial of Los <unk> and patio Scapulohumeral muscular dystrophy.
We're also pleased to announce the appointment of Alex APR to the position of President and Chief Executive Officer, and member of the Board of Directors effective July one 2023.
As of last Friday, Alex joined a special adviser to me and we are thrilled to have a world class leader of his stature onboard to propel program to the next level of achievement.
Alex brings deep industry knowledge from the public sector and has more than 25 years of experience building commercial stage pharmaceutical organizations.
Most recently, Alex served as Chief Executive Officer, and a member of the board of directors of a viral prior to the company's acquisition by Pfizer.
Prior to her a viral Alex served as President Chief Executive Officer, and member of the board of Directors of Dover Pharmaceuticals earlier in his career, Alex spent 10 years as executive Vice President of marketing and sales for United Therapeutics and held it roles of increasing responsibility within the commercial organization.
<unk> at Glaxosmithkline.
Alex This impressive track record makes him an ideal fit for fulcrum at this critical juncture.
With this brief introduction I'll now dive into our programs and provide an update on recent activities.
Let me start by discussing our most recent updates to the Ft X $60 58 program, our oral hbf inducer for the potential treatment of patients with sickle cell disease.
As previously announced.
We received verbal notification from the FDA on February 23rd that they had placed the full clinical hold on the investigational new drug application for <unk> $60 58.
Seeds, a formal clinical hold letter from the FDA on February 24th we immediately suspended dosing and paused enrollment in the trial of FTE at $6 58.
We have been an active and ongoing dialogue with the FDA and we will provide an update once we have more clarity on the regulatory path forward overall, our interactions with the agency, thus far have been productive and collaborative and we look forward to continuing our dialogue as we work to resolve the clinical hold.
And the initial feedback provided in February 2023, the FDA stated that the hold related to preclinical data submitted in April October and December 2022, and non clinical and clinical evidence of hematologic malignancies observed with other inhibitors of Polycom repressor complex, two or PRC too.
The agency is focused on balancing the safety and efficacy tradeoffs and has requested a program further define the population or the potential benefit of continued treatment with MTX $60 58 outweighs potential risk there.
Hold was not a result of any clinical findings in the phase one b trial that was ongoing at the time of the hold.
For further context, we have a strong data set from the subjects, who completed dosing prior to the clinical hold treatment of MTX $60 58, the highest dose of 12 milligram showed a 10% absolute hbf increase from baseline, resulting in a total hbf level of 24, 9% after 42 days of treatment.
Additionally, MTX 60, 58 has been generally well tolerated to date with no drug related treatment emergent serious adverse events or discontinuation due to treatment emergent adverse events.
I'll, let Jeremy subjects showed clinically relevant improvements in the six and 12 milligram dose cohorts consistent across subjects, both on and off background Hydroxyurea. The current standard of care.
We maintain that MTX $60 58 has the potential to provide a differentiated therapeutic option for people living with sickle cell disease and that the clinical and preclinical data generated to date demonstrate a favorable benefit risk profile.
Now turning to our most advanced program <unk>, a selective <unk> 38, Alpha beta mitogen activated protein kinase inhibitor.
<unk> is in phase III development for the treatment of Fsh D and autosomal dominant genetic form of muscular dystrophy, which has an estimated patient population of 16000 to 38000 in the United States alone.
Fsh D is characterized by relentless and accumulating muscle and functional loss and resulted in the inability to perform daily life activities due to a significant impairment of upper extremity function loss of mobility and chronic pain.
Although it is one of the most common forms of muscular dystrophy. There are currently no approved treatments given the high unmet need for innovation. We are extremely encouraged by last map months' therapeutic potential to preserve muscle function and believe it has the potential to address the urgent need for a safe and effective disease model.
<unk> treatment that can slow or stop disease progression.
We initiated reach our double blind placebo controlled phase III trial of <unk> in June 2022, and are currently enrolling patients in the U S, Canada and Europe .
At this time 31 sites are active out of 36 sites.
This 48 week trial is expected to enroll approximately 230 adults and expected to complete enrollment in the second half of 2023.
We are pleased with the rapid pace of enrollment and the last map Mod phase III reach trial, which is both a testament to the high level of engagement by our clinical trial sites and our team's strategic execution.
The primary endpoint is the absolute change from baseline and reachable workspace or our ws a quantitative measure of FERC extremity range of motion and function that specifically evaluates shoulder and proximal arm mobility with three D motion sensor technology.
Preserving this upper extremity function is critical for maintaining the ability for self care and other activities of daily living that directly influence quality of life and independence.
In addition to safety and Tolerability secondary endpoints include muscle fat infiltration or MSI, an important marker of disease pathology and self reported outcomes such as the patient global impression of change or Pgi.
And quality of life measures diesel include health care utilization questionnaires that will inform our thinking about payer strategy as we prepare for a potential commercial launch.
<unk> was designed as a highly efficient 48 week trial and is intended to be registration, enabling both in the U S and ex U S geographies.
We are confident that we have selected reliable measures of disease progression and we hope to demonstrate meaningful advantages for less <unk> compared to placebo.
Encouragingly, our phase <unk> readout for trial demonstrated significant improvements in <unk> relative to placebo at 48 weeks.
Furthermore, topline results from the ongoing open label extension of Readouts for shows that participants in the initial treatment arm, who continued to receive <unk> demonstrated durability of effect through a 96 week period. Additionally, patients who crossed over from placebo to snap a month after the initial <unk>.
88 week trial period showed improvement and slowing of disease progression as measured by our Ws mean change from baseline.
We believe these data support the disease modifying potential and long term benefit of <unk>.
To date <unk> has been dosed in over 3600 patients across multiple therapeutic areas and results from Redux tour and our open label extension trial provides evidence of an encouraging safety and Tolerability profile.
As we drive our clinical path forward for <unk> months, we look forward to leveraging the large safety database and building on our learnings from Redux for an ongoing open label extension trial.
Now turning to other corporate matters as previously announced Esther Raj <unk>, Our Chief Financial Officer recently resigned from the company effective April 21 2023.
We appreciate our commitment to operational and financial excellence and are grateful for the positive contributions she has made to our company.
We are continuing to work with aster in her role as an adviser or the finance team continues to execute our financial strategy.
As a reminder, doctor Ian Frazer continues to serve as interim CFO and Dr. Alan <unk> member of the program Board of Directors. Since February 2017 continues to serve as senior clinical adviser to ensure program continuity.
As we continue to solidify our leadership team, we remain focused on realizing programs mission and the work at hand.
With that I will provide an update on our financials.
We ended March 31, 2023, with cash cash equivalents and marketable securities of $297 8 million.
Imperative $202 9 million on December 31, 2022 and.
In January 2023, we completed an underwritten public offering of our common stock raising approximately $117 3 million in net proceeds.
We continue to operate from a strong financial position and we expect our cash cash equivalents and marketable securities to fund our operating expenses in the mid 2025.
This projection assumes a timely resolution of the FTF $60 50, a clinical hold.
Collaboration revenue was.
Zero point $3 million for the first quarter of 2023 as compared to $2 6 million for the first quarter of 2022.
Research and development expenses were $16 7 million for the first quarter of 2023 as compared to $17 8 million for the first quarter of 2020 to the.
The decrease of $1 1 million was primarily due to decreased research and development head count partially offset by increased costs associated with the advancement of reach.
General and administrative expenses were $11 5 million for the first quarter of 2023 as compared to $10 8 million for the first quarter of 2022.
The increase of <unk> 7 million was primarily due to increased stock based compensation expense.
Net loss was $24 8 million for the first quarter of 2023 as compared to $25 9 million for the first quarter of 2022.
Overall, I am confident the company's strong cash position and upcoming catalysts provide a solid foundation for execution and value creation.
We remain focused on driving our clinical programs forward exploring opportunities to leverage the value of our research engine and executing our corporate objectives.
We remain on track to complete enrollment for our Fsh D phase III reach trial in the second half of 2023 and are committed to working with the FDA to resolve the clinical hold on <unk> $60 58, I want to reiterate that we are optimistic there is a path forward to resolve the full clinical hold. Additionally.
With today's announcement of Alex as our next CEO and President program is ending the first quarter of 2023, and a position of strength and great promise for the future.
Before we conclude today's call I want to extend my sincere appreciation and gratitude for the foundational work that has brought us closer to trading the root cause of genetically defined rare diseases, and bringing transformative therapies to patients.
I'd like to thank the entire fulcrum team, our investors and the many people who have been supportive along the way, including our patients and their families.
With that we're happy to take questions.
To ask a question. Please press star one one on your telephone and wait for your name to be announced.
To withdraw your question. Please press star one one again please.
Please standby, while we compile the Q&A roster.
The first question comes from Edward Chen Tong.
With Piper Sandler your line is open.
Great. Thank you for taking the.
My question.
Robert Thank you for the thorough update I wanted to just dig a touch deeper into to clarify variables.
What are the outstanding issues, what do you see as sort of the experiments you need to do or data you need to collect in order to provide the FDA with the information they need to lift the whole.
Thanks, Chad.
Yes, there is two outstanding issues with the FDA that we're currently in discussions with them.
One is a question around reversibility of effect that we see when we.
All right.
Inhibiting <unk> with <unk> 58, that's primarily related to reverse ability of gene expression changes for <unk> of course are a consequence of inhibiting the EDI.
Protein those those studies are preclinical non toxicology studies.
Along the lines of pharmacologic reversibility, they are well underway.
And as we get those results, we'll be discussing them with.
With the FDA.
The other set.
Outstanding issues relates to defining the.
Patient populations that can most benefit from the elevation in hbf that we're seeing.
Yes.
Regulatory agency has asked us to define that population.
A higher risk population than we were evaluating previously and we're in active discussions with them to discuss that that population.
As I'm sure you know there have been a number of different definitions of at risk populations in sickle cell patients for the year looking at the gene and cell therapy studies or some of the other small molecules that are symptomatic treatments and so we're integrating those prior studies along with our own thoughts carrier to define that population that can most benefit.
Right.
Yes that makes a lot of that one last quick question, if I may and this might be a tough one to answer is there a dose relationship to the concerns that the FDA pause or census, really clinical finding.
They're not some kind of dose orally.
Our relationship.
Tox concerns.
Yes, so we have not seen anything in the clinical studies that would.
It gives us any concern about about.
Toxicology findings that had been the same trade clinically.
As I mentioned during the update.
The two six and 12 milligrams clinical doses there have been no no serious adverse events.
At all in terms of the preclinical studies, we see dose dependent increases in target engagement.
<unk>.
Part of the Fda's concern around the hematologic malignancies that we've seen is is that those types of malignancies have been seen with other PRC two inhibitors and then you wanted to be sure that we're defining that.
Risk benefit ratio appropriately both pre clinically as well as clinically.
That's super helpful. Robert If I may just take Tom Congrats on funding and the CEO of great job stepping in during this sort of a transition time for the company.
Thanks.
Please standby for the next question.
Okay.
The next question comes from Joseph Schwartz with SBB Securities. Your line is open.
Thanks, So much I was wondering if you have any data on hand, which can help distinguish the propensity of fts $60 58.
Cause heme malignancies relative to other PRC <unk> inhibitors that youre able to show to the FDA in order to help them get comfortable with the risk benefit of <unk> in sickle cell disease and as a follow up how are you thinking about.
Defining the patient population, who can benefit and does that high risk.
Thanks, Joe maybe I'll take the first part of that first question that you asked and then let <unk> speak to the second defining the patient population.
Among the data that we've been able to share with the FDA. It is of course not only.
The studies that we've done.
Toxicology studies that we've done but also the gene expression changes that we're seeing with <unk> inhibition.
In the animal studies.
Particularly at most.
Townes model animal studies, what we've seen there is that there is a.
There obviously are a number of gene expression changes.
We're seeing really as you would expect robust.
On the <unk>.
Okay.
Hbf gene in HBV.
And that and that that's what the FDA is really focused on in terms of the reverse ability studies.
And so those kinds of gene expression changes relative to other inhibitors of PRC two are what they are focusing on.
And maybe you want to speak to defining the patient population yes.
Thanks, Robert and Thanks, Joseph for the question.
So based on the clinical data that we've generated to date.
We've been able to see the subjects treated with <unk> hundred 68.
Experienced a dose dependent and clinically relevant increase in their fetal hemoglobin into the range, where we think that this is going to be clinically relevant.
Potentially beneficial.
We will discuss these aspects with the FDA as we explore forward and as we think about.
Populations for the clinical trial, we have been informed greatly by therapies in the field, including.
Gene therapies and stem so.
Placement therapies gene editing and so on where a higher risk population has been defined in those studies.
Yes.
Okay.
Okay.
Please standby for our next question.
The next question comes from Madhu Kumar with Goldman Sachs. Your line is open.
Okay. This is rob on for Madhu, Thanks for taking our questions and we were just wondering are there any.
Thoughts to new asset R&d's, given your cash runway.
Thanks, Rob.
Actually under the leadership of our Chief Scientific Officer, Jeff Jacobs J J as he goes by.
Got it.
A number of options that are progressing through the pre clinical.
Programs, we're not quite ready to give updates on the status of those programs and where the areas, but we continue to be focused on.
Non malignant hematology space in the muscular dystrophy <unk> space.
And as Alex comes onboard and has a chance to come up to speed on those programs. We're.
We're excited about providing further updates on what those programs are in their development status.
Okay is there a timeline that we can expect for sort of communication of the new <unk>.
No im not yes, it's a little premature for us to speculate on their already provide guidance on those timelines.
Okay. Thank you.
Please standby for the next question.
The next question comes from Matthew Biegler with Oppenheimer. Your line is open.
Hey, Rob and team. Thanks for the question. We were just curious on timelines do you still think that six month timeline to a possible resolution is still on the table or it looks likely that 2020 our events.
As far as we are continuing the ongoing dialogue with the FDA, it's a little early to provide.
Clear definition of appointment timeline.
Well get resolved certainly we're in active conversations are really been encouraged by the dialogue that we're having with them.
The interaction with them as core Joe and very very active so our current guidance.
It is.
Assuming a <unk>.
Rapid resolution of that that timeline.
Exactly when that will get resolved.
I don't want to guide to yet.
Okay. That's fair I wanted to maybe dial until that all but a little bit more into what you just said about your interactions with the FDA.
Would you describe them are they ongoing and collaborative or are you kind of just working now behind the scene.
As you said defined an eligible patient population and then Ron some of the other non toxicology.
Or is this like.
Very cordial relationship that you have thanks.
Thanks.
Yes, its actually extremely core Joe with the regulatory agency.
<unk>.
<unk> discussed.
Various thoughts with them.
It's been a true partnership with them with with.
Real real <unk>.
And discussion around their perception of the populations, which coincides with our perception of the populations that are at risk and it's not contentious anyway.
Actually a pleasure interacting with them as they provide guidance and thoughts on the population.
Thanks, Rob.
As a reminder to ask a question. Please press star one one on your telephone.
And wait for your name to be announced.
Please standby for our next question.
Yes.
The next question comes from Judah Frommer with Credit Suisse. Your line is now open.
Yes, hi, good morning, Thanks for taking the questions first just curious from a clinical study perspective does.
<unk> the risk profile of that potentially addressable patient population.
Kind of deep value any of the data you have thus far or is there or is it more just about the commercial risk benefit profile here.
Yes, let me speak to the last part of that the commercial value and then let <unk> speak to the first part of the question.
So it doesn't add any value of the data we have in hand.
And this and this these initial studies defining a higher risk population.
As the FDA has requested first of all.
We think growth.
Based on data we have in hand, we will continue to see the robust increases in hbf.
We've seen up to date.
More importantly than that.
The study they are requesting us to do first and that really doesn't speak subsequent studies that we'd be doing that we'd be looking at the overall commercial opportunity.
Our oral small molecule activator of Hbf would treat things still has an important place in the pharmacopeia.
As you know in overall commercial strategy often involves multiple kinds of trials in multiple kinds of patients and this is just.
First foray into a higher risk population, maybe I'll, let ian speak to weather.
The applicability of the data we've generated to date.
Yes.
Robert and thanks to two so I think in no way at all does this devalue or alter our perceptions of the data that we've generated to date in the sickle cell patient population.
At doses up to six and 12 milligrams once daily.
Yes.
Population clearly.
Is that an affected sickle cell population some of them were.
Also on concomitant hydroxyurea at the time and we've seen robust increases in fetal hemoglobin in that population. So as we as we move forward into <unk>.
Somewhat slightly different defined patient population.
Think that theres any impact or or adverse.
Effects related to the previous data.
Yes.
Okay.
Is it fair to assume that if youre going up again.
<unk>.
Cell therapy type approaches that you'd potentially be dosing higher to arrive at.
Higher levels of Hbf induction in a higher risk population or is your sense that again.
Which I know has been an area of contention historically, 10% absolute induction bar might still be relevant in this higher risk population.
Yes. Thanks.
The.
I don't think we see ourselves going against a gene therapy and gene editing.
We're using the way that they've defined patient population does it is a guideline as we move forward.
To define a patient population bearing in mind that those procedures are associated with significant risks.
Themselves. So just a clarification there on how we're thinking of those particular populations.
Think there's any any bar on how much hbf induction, where looking forward I think clearly as you've mentioned that the 10 is the number that's been thrown out there I think in terms of the absolute percents, but are hopeful getting into the range of 20% to 30% is clearly being associated.
With with clinical benefit using.
Genetic or pharmacological or a combination of those two.
Approaches in the past and so I think getting into that range seems to be fairly beneficial.
30.
30% in a little higher might be functionally cured.
In some extent to some extent.
So we will be evaluating the dose response as we move up.
Potentially beyond 12 milligrams to evaluate.
The dose response on Hbf.
That's helpful. Thank you.
Okay.
This concludes our question and answer portion of the call I will now turn the call back over to Fulcrum CEO Robert for closing remarks Robert.
Thank you operator, and thanks to everyone, who joined US. This morning, please stay safe and healthy.
And I'm sure we'll be talking to you all later thanks Ken.
Hi.
Thank you for participating you may now disconnect.
Goodbye.
Okay.
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